Human mononuclear leukocytes produce a growth factor (HGF) for hybridoma and plasmacytoma cells. HGF has recently been proven to be identical to IFN-beta 2, 26-kDa protein and BSF-2. HGF can be quantitated in a proliferation assay with the HGF-dependent hybridoma cell line B13.29. By selection of an extremely sensitive variant of this cell line, we were able to measure HGF production of single cells. Limiting dilution analysis of the producing cells in combination with size, density and adherence characteristics showed that HGF is produced by monocytes and not by lymphocytes. There was no need for the monocytes to be stimulated but the cells did require the presence of serum. This serum requirement could be met by purified bovine serum albumin, but not by other proteins like ovalbumin or human gamma-globulin. HGF production in vitro by monocytes starts after 2 h of incubation and is completed within 24 h.

SummaryThe role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n --4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase-oll-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment FI+ 2 and thrombin-antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-c~2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin-induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees.

C. luciliae are hemoflagellates nonpathogenic for man and easy to culture. They have a giant mitochondrion, in which the mitochondrial DNA is concentrated in a single large network, the kinetoplast. When used as a substrate for the indirect immunofluorescence technique, studying sera from patients with SLE, we could demonstrate a very good correlation between this test and the Farr assay for the demonstration of antibodies to double-stranded DNA. Although the sensitivity of both techniques is on the same order of magnitude, the IF technique has the following advantages over the Farr assay. It is easy to perform in laboratories equipped for autoimmune serology. It possesses an intrinsic check on the immunoglobulin character of the DNA-binding activity. It allows one to determine the Ig classes and subclasses of antibodies to DNA. It permits study of complement fixation to antibodies without interference of Clq fixation to DNA or anticomplementarity of the serum. There is an absence of interference with antibodies to single-stranded DNA.

Human monocytes produce a number of soluble mediators involved in regulation of inflammation and lymphocyte growth and differentiation such as interleukin 1 (IL 1) and tumor necrosis factor. Recently, the cDNA of another monocyte-derived factor, interleukin 6 (IL 6), was cloned. Herein we show that purified E. coli-derived recombinant IL 6 (rIL 6) is as active as IL 1 in the thymocyte assay. In addition, IL 1 and IL 6 synergize strongly in stimulating thymocyte proliferation. Another property shared by IL 1 and IL 6 is their pyrogenicity. Human rIL 6 induces a monophasic fever after i.v. injection into rabbits. Together with the observation that IL 1 induces IL 6 in a variety of cells including thymocytes, our data suggest that IL 6 is involved in many of the pleiotropic effects of IL 1.

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Background: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. Objective: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. Methods: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. Results: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both nonresponders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. Conclusion: Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.